The story of living in spite of melanoma, metastasis, vaccines, anti-PD-1, lung removal, and stereotactic radiation. The story of life with family and friends. {Posts under ~ Sew Chaotically, Travel Chaotically, and Chaotic Cookery also housed within! A girl's gotta have fun!}

About Me

Who am I? That is a question the rest of you could probably answer better than I. I am a wife, mother, daughter, sister, friend, pediatric nurse practitioner, cook, teacher, gardener, lover of words and music, occasional seamstress, and homemaker. I do have a couple of talents of questionable merit: I can create a decent meal in less than 30 minutes. I can feed and/or soothe almost any baby. And I can remember practically any song I've ever heard. For the rest, I'd rather those who know me decide.

There has been considerable progress
in treating malignant melanoma over the last few years. The
immune-checkpoint-inhibitors nivolumab and pembrolizumab have been
approved by the Food and Drug Administration in 2014 for the therapy
of metastatic melanoma. Anti-programmed cell death-1-blocking
antibodies are known to cause immune-related adverse events.
Physicians should be aware of common and rare side effects and pay
attention to new ones. We therefore report a severe and
life-threatening side effect of anti-programmed cell death-1
immunotherapy with nivolumab that has not been previously reported:
the development of a third-degree atrioventricular block. After a
second infusion with nivolumab, our patient developed a troponin
I-positive and autoantibody-positive myositis and a few days later a
new-onset third-degree atrioventricular block. This is most likely
because of an autoimmune-induced myositis with a cardiac impairment
in terms of a myocarditis, which led to an impairment of the
conduction of cardiac electrical stimuli.

Two
cases of clinical myasthenia gravis associated with pembrolizumab use
in responding melanoma patients.
Nguyen, Kuo, Budiman, Christie. Melanoma
Res. 2017 April.Immune
checkpoint inhibitors have changed the landscape of the treatment of
multiple solid malignancies, and have been used increasingly in the
recent years. Although usually well tolerated, given the relative
inexperience of using immune checkpoint inhibitors, we are still
learning of new side effects from the treatment. We report on two
cases of ocular myasthenia gravis that occurred after treatment with
pembrolizumab, an antiprogrammed-death (anti-PD1) monoclonal antibody
for advanced melanoma in responding patients. One case is in an
81-year-old man and the second case in an 86-year-old woman, both
with BRAF-negative metastatic melanoma receiving pembrolizumab. These
two cases of ocular only associated myasthenic syndrome appeared 7
and 11 weeks after the initiation of pembrolizumab. We conclude that
the condition is most likely associated with pembrolizumab as
symptoms started after treatment with pembrolizumab, neither patient
had other evidence of neurological cause for presentation, and
symptoms also improved rapidly with administration of steroids. Both
patients showed good oncological response to anti-PD1 treatment and
one patient successfully continued to receive ongoing treatment with
no further complications.PD-1
inhibitors increase the incidence and risk of pneumonitis in cancer
patients in a dose-independent manner: a meta-analysis. Wu, Hong,
Zhang, et al. Lancet
Oncol. 2017 Mar 3.

Therapies
that targeted PD-1 have shown remarkable rates of durable clinical
responses in patients with various tumor types. However, the extent
and knowledge of pulmonary toxicities associated with PD-1 blockade,
mainly manifested as pneumonitis, remains obscure. In this study, a
total of 6360 subjects from 16 phase II/III clinical trials were
pooled for meta-analysis to evaluate the overall incidence and risk
of PD-1 inhibitors-related pneumonitis in cancer patients. The
incidence of pneumonitis during anti-PD-1 immunotherapy was 2.92%
for all-grade and 1.53% for high-grade pneumonitis. Compared with
routine chemotherapy, PD-1 inhibitors were associated with a
significant increased risk of pneumonitis. Moreover, among the types
of tumor treated with PD-1 inhibitors, the melanoma patients have the
lowest incidence of pneumonitis, while the non-small cell lung cancer
(NSCLC) and renal cell carcinoma (RCC) patients have the highest.
Furthermore, no significant differences were detected in the
incidences of all- and high-grade pneumonitis between high-dose and
low-dose groups of PD-1 inhibitors. In conclusion, PD-1 inhibitors
were probably associated with an increased risk of pneumonitis in a
dose-independent manner, compared with routine chemotherapeutic
agents. The frequency and severity of treatment-mediated pneumonitis
was quite different in patients with various tumor types.

Immune
checkpoint inhibitors such as Pembrolizumab are used to restore
antitumour immune response. It is important to be vigilant of immune
mediated adverse events related to such therapy. We report a case of
autoimmune limbic encephalitis with Contactin-Associated Protein-like
2 (CASPR2) antibody secondary to Pembrolizumab therapy for metastatic
melanoma.

Ipilimumab
(a monoclonal antibody against CTLA-4) and nivolumab (a humanized
antibody against PD-1) target these immune checkpoint pathways and
are used for treatment of melanoma and an increasing number of other
cancers. However, they may cause immune-related adverse effects
(IRAEs). Although many endocrinopathies are known to be IRAEs,
primary hypoparathyroidism with severe hypocalcemia has never been
reported. This is the first case of hypoparathyroidism as an IRAE
presenting to an Emergency Department with acute hypocalcemia. A
73-year-old man with metastatic melanoma presented to the Emergency
Department for the chief complaints of imbalance, general muscle
weakness, abdominal pain and tingling in extremities. He had wide
spread metastasis, and begun immunotherapy with concurrent ipilimumab
and nivolumab 1.5months ago. At presentation, he had ataxia,
paresthesia in the hands and feet, and abdominal cramping. Magnetic
resonance imaging of the brain was unremarkable. He was found to be
hypocalcemic with undetectable plasma parathyroid hormone. He was
admitted for treatment of symptomatic hypocalcemia and was diagnosed
with primary hypoparathyroidism. Shortly afterwards, he had
thyrotoxicosis manifesting as tachycardia and anxiety, followed by
development of primary hypothyroidism. At 4months after the Emergency
Department visit, his parathyroid function and thyroid function had
not recovered, and required continued thyroid hormone replacement and
calcium and vitamin D treatment for hypocalcemia. Primary
hypoparathyroidism caused by ipilimumab and nivolumab may acute
manifest with severe symptomatic hypocalcemia. Emergency care
providers should be aware of hypoparathyroidism as a new IRAE in this
new era of immuno-oncology.

Be safe. Be aware. Seek help if you think you need it! Hang tough, ratties! Hang tough! - c